BIDN, a bicyclic dinitrile convulsant, selectively blocks GABA-gated Cl- channels.
BIDN (3,3-bis(trifluoromethyl)bicyclo[2,2,1]heptane-2,2-dicarbonitrile) at 10(-5) M blocked GABA-induced inhibitory postsynaptic potentials (IPSPs) recorded from an identified, giant interneuron (G12) of the cockroach (Periplaneta americana). The same concentration of this bicyclic dinitrile also blocked Cl- -mediated responses of G12 to GABA applied by pressure microinjection into the terminal abdominal ganglion neuropile containing dendrites of G12. BIDN (10(-5) M) was without effect on a response of G12 to GABA known to be mediated by a GABAB type receptor. In studies of the cell body of an identified motor neurone, the fast coxal depressor (Df) in the cockroach metathoracic ganglion, BIDN (10(-5) M) blocked reversibly an extrasynaptic GABA-gated Cl- channel, but not an extrasynaptic L-glutamate-gated Cl- channel. Glycine-gated Cl- channels observed when rat brain messenger RNA was expressed in Xenopus laevis oocytes were unaffected by BIDN at concentrations up to 10(-4) M, whereas this same concentration of BIDN completely blocked GABA-gated Cl- responses recorded from the same preparations. Unlike picrotoxin, which antagonises a variety of ligand-gated Cl- channels, to date BIDN has been found to block only Cl- channels gated by GABA, both in insect and vertebrate preparations.
Hamon
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Laboratoire de Neurophysiologie, CNRS-ER 120, Université d'Angers, France.
Le Corronc
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Hue
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Rauh
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JJ
Sattelle
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DB
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D003292:Convulsants / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology*; D007395:Interneurons / Q000187:drug effects; D015640:Ion Channel Gating; D008297:Male; D008845:Microinjections; D009570:Nitriles / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects; D010526:Periplaneta; D012333:RNA, Messenger / Q000494:pharmacology; D051381:Rats; D014982:Xenopus laevis; D005466:Fluorocarbons
D001643:Bridged Bicyclo Compounds; D018118:Chloride Channels; D003292:Convulsants; D018756:GABA Antagonists; D009570:Nitriles; D012333:RNA, Messenger; C098123:3,3-bis(trifluoromethyl)bicyclo(2.2.1)heptane-2,2-dicarbonitrile; D005466:Fluorocarbons